Heterogeneity of oral tolerance defects in autoimmune mice

Michael L. Miller*, John S. Cowdery, Carl A. Laskin, Michael F. Curtin, Alfred D. Steinberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Three strains of mice, BXSB, MRL- lpr lpr, and NZB, which spontaneously develop autoimmune syndromes, all fail to become tolerant to challenge with bovine γ-globulin (BGG) in adjuvant by prior intraperitoneal (ip) injection of BGG in tolerogenic form. In the present study, these three strains were examined for the ability of a single enteric dose of BGG or ovalbumin (OVA) to tolerize to subsequent challenge with the corresponding antigen in adjuvant. In contrast to lack of ip tolerance to BGG, BXSB mice were tolerant to gastrointestinal (GI) BGG as well as to GI OVA, suggesting that ip and GI forms of tolerance to BGG operate through distinct mechanisms in these mice. MRL- lpr lpr mice had normal tolerance to GI OVA but not GI BGG. The presence of enteric tolerance to one antigen but not another suggests that the responsible cellular defects vary from one antigen to another. NZB mice lacked tolerance to both GI BGG and GI OVA. Splenectomy of NZB mice allowed normal tolerance to enteric BGG; spleen cells administered to splenectomized NZB mice interfered with BGG tolerance. Congenic NZB.xid mice were tolerant only to OVA. These results suggest that in NZB mice Lyb 5+ cells interfere with tolerance to enteric OVA and Lyb 5- spleen cells interfere with tolerance to enteric BGG.

Original languageEnglish (US)
Pages (from-to)231-240
Number of pages10
JournalClinical Immunology and Immunopathology
Issue number2
StatePublished - 1984

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology


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